In this proposal we plan to continue examining the role of serotonin (5-hydroxytryptamine, 5-HT) in the descending control of medullary and spinal dorsal horn neurons. An isolated (in vitro) brainstem - spinal cord preparation of the frog will be used as a model to study the mechanism(s) by which 5-HT might act as a transmitter or modulator in the dorsal horn. Intracellular recordings will be attempted in order to examine the effects of 5- HT on the resting and dorsal root-evoked membrane potential and input resistance of the dorsal horn neurons. An estimate of the reversal potential and ionic dependence of the 5-HT produced effects is also attempted, as will an examination of the effects of 5-HT antagonists, synaptic transmission blockade, and interaction with other putative transmitters (e.g., glutamate). Subsequently, an attempt will be made to correlate the 5-HT-induced effects with those produced by electrical stimulation of brainstem sites giving rise to the descending 5-HT pathways in order to determine whether the two act through identical mechanisms (i.e., whether 5-HT meets the "identity of action" criterion). Additionally, the effects of both 5-HT application and brainstem stimulation will be examined to determine whether they modify a ventral root potential that might be an index of nociceptive behavior. Finally, the effects of norepinephrine will be examined in precisely the same way as for 5-HT. The proposal should increase our knowledge of nociception at medullary and spinal levels, and this knowledge might lead to significant advances in dental and cutaneous pain management.